3. Diabetic nephropathy
What the renal corpuscle should look like!
4/23/2015 2
Diabetic Glomerulosclerosis
Proliferation of mesangial cells and acellular
mesangial tissues.
4/23/2015 3
Diabetic Glomerulosclerosis
Mesangial and endothelial cell proliferation
4/23/2015 4
Diabetic Nephropathy and Diabetic Nephropathy and
AlbuminuriaAlbuminuria..
1. Hyperfiltration
2. Microalbuminuria (albuminuria 30-
300mg/day)
3. Overt nephropathy (albuminuria
>300mg/day) - Relentless decline in renal function
(untreated 1ml/min/month)
– Hypertension
– Increase in CVD
4. End stage renal failure
4/23/2015 5
What histological and physiological
changes occur?
• Glomerulosclerosis
• People with diabetes have increased
predisposition to renal infections (more
glucose in urine) and papillary necrosis
• Arterial hypertension – leads to formation
of hyaline layer in afferent arterioles –
narrows lumen – increase BP.
4/23/2015 6
4/23/2015 7
Podocyte injury
• It is likely that damage to the glomerular
capillaries and the podocyte lead to
glomerulosclerosis.
4/23/2015 8
Micro-vascular disease
• Many people with diabetes develop both
retinopathy and nephropathy
• Similar damage has been reported in both the
retinal capillaries and the glomerular capillaries.
• Damage to the glomerular fenestrations and
podocytes reduces glomerular filtration and
allows protein to appear in the urine
• Reduced GFR and proteinurea are signs of
nephropathy
4/23/2015 9
Nephropathy and CV complcations
• Hypertension and proteinuria lead to progressive loss of functional renal tissue, and ultimately end stage renal failure.
• Collins et al. (2005) argue most people with chronic renal disease die of CV complications because the nephropathy exacerbates other CV conditions.
• As kidney fails, BP is increased in an attempt to
maintain GFR.
4/23/2015 10
Albumin in urine
• Macroalbuminuria
• Over 300 mg/litre of
urine
(0ver 300 mg excreted
per day)
Overt nephropathy
• Micoabuminuria
• Under 300 mg/litre or
urine
(between 30 and 300
mg excreted per day)
4/23/2015 11
Part of annual check up
• Within the NHS an assessment of
microabuminuria has been introduced as part
of the annual check up for all patients who do
not prove positive for proteinuria with a
'dipstick’
4/23/2015 12
Screening for albuminuria
• Most convenient test is ACR
• Early morning urine preferred
• Normal range is:
– <2.5 mg/mmol (male)
– <3.5 mg/mmol (female)
• Exclude UTI, fever, heavy exertion
• If normal repeat at 1 year
4/23/2015 13
•Stage 1: Normal GFR > 90 ml/min
•Stage 2: Early CKD GFR 60-89 ml/min
•Stage 3: Moderate CKD GFR 30-59 ml/min
•Stage 4: Severe CKD GFR 15-29 ml/min
•Stage 5: End-stage renal disease GFR
below 15ml/min
Stages of Kidney disease related to GFR
4/23/2015 14
What can be done?What can be done?
• Prevent people developing type 2 DM (targeting high risk groups – lifestyle modification)
• Prevent diabetic patients developing microalbuminuria
• Prevent microalbuminuric patients developing overt nephropathy
• Slow progression of diabetic nephropathy
• Cardiovascular risk factor management
4/23/2015 15
Glycosylated Haemoglobin Glycosylated Haemoglobin
and Controland Control
Mulec NDT 1998
4/23/2015 16
Diabetic Nephropathy: Diabetic Nephropathy:
Cardiovascular DiseaseCardiovascular Disease
• Cardiovascular disease is the commonest cause of death in people with diabetes
• The presence of proteinuria increases the risk substantially
• Up to 70% of deaths in patients with diabetic nephropathy – vascular disease
4/23/2015 17
Cardiovascular ProtectionCardiovascular Protection
• Glycaemic control
– UKPDS – intensive (HbA1c 7.0%) vs
conventional (HbA1c 7.9%)
– For each 1% reduction in HbA1c – 21%
reduction in deaths related to DM
• 12% reduction in any endpoint related to
diabetes
• 25% reduction in microvascular disease
• Metformin offered greater protection4/23/2015 18
4/23/2015 19
Sign 116
Conclusions for diabetic Conclusions for diabetic
nephropathynephropathy
• Diabetic nephropathy is common
– Renal aspect
– Cardiovascular aspect
• These patients are high risk individuals
4/23/2015 20
Conclusions for diabetic Conclusions for diabetic
nephropathy (continued)nephropathy (continued)
• Patients with diabetes – must identify
microalbuminuria early - SCREEN urine
• When there are early warning signs of high
risk individuals - advocate– Good glycaemic control
– Control BP
– Use of ACE inhibitors
– Encourage healthy lifestyle – diet, exercise, stop smoking
4/23/2015 21
Conclusions for diabetic Conclusions for diabetic
nephropathy (continued)nephropathy (continued)
• Diabetic renal disease – overt nephropathy
– Intensively manage BP, lipids, glycaemic
control, stop smoking
– Use of ACE inhibitors and ARBs
– Promote healthy lifestyle – exercise and
healthy eating
– Sodium restriction (urinary <150mmol/day)
– Consider protein restriction4/23/2015 22
4. Skin disorders Acanthrosis nigrans
in diabetes mellitusHigh levels of insulin cause the skin to become
discolored and velvety in texture, a condition
called acanthrosis nigricans. This is common in
people with darker skin who have type 2
diabetes, including African Americans, Native
Americans, and people of Hispanic origin.
Acanthrosis nigricans "is a thickening and a
darkening of the skin, typically around the neck,
in the underarms, and in the groin,” adds
Einhorn. “It’s quite a specific indicator of insulin
resistance --. It is definitely a warning sign---”
23
24
5. Depression
• Many people with diabetes suffer
additionally because of depression.
• Depression appears to increase the risk of
developing severe complications
Lin et al. (2010), Diabetes Care.
6. Pregnancy related complications
St. Vincent Declaration
‘Achieve pregnancy outcome in the diabetic
woman that approximates that of the
non-diabetic woman’
Have We Succeeded?
• Congenital malformation rate 4-10 fold higher.• Perinatal mortality rate 4-7 fold higher.• Stillbirth 5 times more common.• Babies 3 times more likely to die in the first 3
months of life.• Maternal Mortality Rate 0.1-0.5% compared to
0.01% for a non-diabetic mother
Diabetes should be regarded as teratogenic
With thanks to Andy Gallagher
Diabetes and pregnancy
Basic potential problems if mother has diabetes:
•Maternal blood has high glucose level therefore foetus will grow too fast and hence macrosomia.
•If baby is delivered after receiving high glucose levels via the placenta, (s)he is faced with a sudden drop in glucose in his/her body.
What should be done.
1. Pre-pregnancy counselling
• Discussion of risks and proposed management strategy
• Diet & lifestyle advice
• Smoking cessation
• Assessment and management of diabetes complications
• Good glycaemic control
• BP control
• Folic acid to be taken
What should be done
2. Management during pregnancy
• Regular check-ups – every two weeks until 30
weeks then weekly
• Fundoscopy each trimester
• Ultrasound 18-20 weeks
• Plan labour
Be proactive when a man presents
with ED. Use comments such as ‚
many men with diabetes discover
they experience problems with
having an erection. If you ever
experience that problem let me
know as there are a number of
avenues we can explore.
7. Erectile Dysfunction
(with thanks to John MacCoid)
Many people with SD still aren’t talking
to their physician
Ipsos Survey 2008.http://www.menshealthnetwork.org/library/EDsurvey2008.pdf
- 38% of men had never talked to a physician about their SD
- Of those men who had spoken to
their physician, 86% initiated the
conversation themselves
Where are the women ?
Treatments available
• Oral – Viagra, Cialis, Levitra
• Intra-urethral – Medicated Urethral System for Erection (MUSE)
• Intra-cavernosal – Caverject
The above are the brand names
Vacuum Erection Vacuum Erection
DevicesDevices
Inflatable Penile
Prosthesis
35
To think about over lunch!
The devil has put a
penalty on all things we enjoy
in life. Either we suffer
in health or we suffer
in soul, or we get fat!
• Albert Einstein (1879 – 1955)
35
36
Cheers !
37
Thank you for your attention
Any questions?
Please email me ([email protected]) if you do not
understand anything or think of something you need to
clarify but remember I am part-time.
Recommended
